[Oncological outcomes of laparoscopic radical trachelectomy for early stage cervical cancer].

Objective: To analyze and summarize the oncological outcomes after laparoscopic radical trachelectomy (LRT) for early stage cervical cancer. Methods: The clinical data and follow-up results of 148 patients with early stage cervical cancer who underwent LRT in Renji Hospital, School of Medicine, Shanghai Jiao Tong University from July 2014 to June 2023 were collected, while tumor outcomes and postoperative pregnancy were analyzed retrospectively. Results: (1) General situation: the median age of 148 patients with LRT was 33 years (range: 19-42 years). Pathological type: 111 cases of squamous cell carcinoma, 36 cases of adenocarcinoma, 1 case of adenosquamous carcinoma. International Federation of Gynecology and Obstetrics (2018) stage: 17 cases of stage Ⅰa1 with lympho-vascular space invasion, 25 cases of stage Ⅰa2, 102 cases of stage Ⅰb1, and 4 cases of stage Ⅰb2. (2) Tumor outcomes: 148 patients were followed up regularly after LRT, and the median follow-up time was 59 months (range: 2-104 months). During the follow-up period, 5 cases of tumor recurred (including 1 death), and the median recurrence time was 10 months (range: 4-33 months). Among them, there were 3 cases of pelvic metastasis, 1 case of distant metastasis, and 1 case of both pelvic and distant metastasis. Both 3-year and 5-year disease-free survival rates of 148 patients were 94.5%, and the 5-year overall survival rate was 98.9%. (3) Postoperative pregnancy: among 148 patients with LRT, 67 patients had pregnancy requirements, followed up for 1 year, and 20 of them were pregnant, with a pregnancy rate of 29.9% (20/67). Among the 20 pregnant patients, 2 cases early abortion, 1 case mid-term abortion, and 17 cases gave birth (including 4 cases of premature birth and 13 cases of full-term birth). Conclusion: Under the condition of strict control of surgical indications, guaranteed surgical scope and tumor-free operation, LRT in patients with early cervical cancer has a good outcome.

[Plurihormonal PIT1-lineage pituitary neuroendocrine tumors: a clinicopathological study].

Objective: To investigate the clinicopathological characteristics of plurihormonal PIT1-lineage pituitary neuroendocrine tumors. Methods: Forty-eight plurihormonal PIT1-lineage tumors were collected between January 2018 and April 2022 from the pathological database of Sanbo Brain Hospital, Capital Medical University. The related clinical and imaging data were retrieved. H&E, immunohistochemical and special stains were performed. Results: Out of the 48 plurihormonal PIT1-lineage tumors included, 13 cases were mature PIT1-lineage tumors and 35 cases were immature PIT1-lineage tumors. There were some obvious clinicopathological differences between the two groups. Clinically, the mature plurihormonal PIT1-lineage tumor mostly had endocrine symptoms due to increased hormone production, while a small number of immature PIT1-lineage tumors had endocrine symptoms accompanied by low-level increased serum pituitary hormone; patients with the immature PIT1-lineage tumors were younger than the mature PIT1-lineage tumors; the immature PIT1-lineage tumors were larger in size and more likely invasive in imaging. Histopathologically, the mature PIT1-lineage tumors were composed of large eosinophilic cells with high proportion of growth hormone expression, while the immature PIT1-lineage tumors consisted of chromophobe cells with a relatively higher expression of prolactin; the mature PIT1-lineage tumors had consistently diffuse cytoplasmic positive staining for keratin, while the immature PIT1-lineage tumors had various expression for keratin; the immature PIT1-lineage tumors showed more mitotic figures and higher Ki-67 proliferation index; in addition, 25.0% (12/48) of PIT1-positive plurihormonal tumors showed abnormal positive staining for gonadotropin hormones. There was no significant difference in the progression-free survival between the two groups (P=0.648) by Kaplan-Meier analysis. Conclusions: Plurihormonal PIT1-lineage tumor belongs to a rare type of PIT1-lineage pituitary neuroendocrine tumors, most of which are of immature lineage. Clinically increased symptoms owing to pituitary hormone secretion, histopathologically increased number of eosinophilic tumor cells with high proportion of growth hormone expression, diffusely cytoplasmic keratin staining and low proliferative activity can help differentiate the mature plurihormonal PIT1-lineage tumors from the immature PIT1-lineage tumors. The immature PIT1-lineage tumors have more complicated clinicopathological characteristics.

A deep-learning model using enhanced chest CT images to predict PD-L1 expression in non-small-cell lung cancer patients.

AIM: To develop a deep-learning model using contrast-enhanced chest computed tomography (CT) images to predict programmed death-ligand 1 (PD-L1) expression in patients with non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: Preoperative enhanced chest CT images and immunohistochemistry results for PD-L1 expression (<1% and ≥1% were defined as negative and positive, respectively) were collected retrospectively from 125 NSCLC patients to train and validate a deep-learning radiomics model (DLRM) for the prediction of PD-L1 expression in tumours. The DLRM was developed by combining the deep-learning signature (DLS) obtained from a convolutional neural network and clinicopathological factors. The indexes of the area under the curve (AUC), integrated discrimination improvement (IDI), and decision curve analysis (DCA) were used to evaluate the efficiency of the DLRM. RESULTS: DLS and tumour stage were identified as independent predictors of PD-L1 expression by the DLRM. The AUCs of the DLRM were 0.804 (95% confidence interval: 0.697-0.911) and 0.804 (95% confidence interval: 0.679-0.929) in the training and validation cohorts, respectively. IDI analysis showed the DLRM had better diagnostic accuracy than DLS (0.0028 [p<0.05]) in the validation cohort. Additionally, DCA revealed that the DLRM had more net benefit than the DLS for clinical utility. CONCLUSION: The proposed DLRM using enhanced chest CT images could function as a non-invasive diagnostic tool to differentiate PD-L1 expression in NSCLC patients.

[Clinicopathological characteristics of H3K27-altered diffuse midline glioma and evaluation of NTRK as its therapeutic target].

Objective: To investigate the clinicopathological characteristics of H3K27-altered diffuse midline glioma (DMG), and to analyze DMG's prognostic factors, and subsequently, to study the possibility of using NTRK as a therapeutic target for DMG. Methods: A total of 232 DMG diagnosed at the Sanbo Brain Hospital, Capital Medical University, Beijing, China from July 2016 to March 2021 were collected. Their clinical, radiological and pathological features, the ratio of MGMT promoter methylation, expression of NTRK, and characteristics of NTRK gene fusion were analyzed. The prognostic values of different factors were also studied, including age, tumor location, histological grade, gene and protein expression of NTRK, and postoperative adjuvant therapy. Results: Among the 232 DMG cases, there were 8 patients with both primary and relapse tumors on the record. Thus, a total of 224 patients were analyzed, including 118 males and 106 females. There were 126 adults (>18 years of age) and 98 children (≤18 years of age). Notably, the most frequent location was thalamus (41/126, 32.5%) in adults, but brainstem (59/96, 60.2%) in children. The lesions showed T1 hypointensity or isointensity, and T2 hyperintensity. However, contrast enhancement patterns of the tumors varied, with many tumors lacking contrast-enhancing. The histological grades included grade 2 (9/224, 4.0%), grade 3 (41/224, 18.3%) and grade 4 (174/224, 77.7%). Two hundred and twenty-four DMGs were diffusely positive for H3K27M and negative for H3K27me3. The ratio of MGMT promoter methylation was low (1/45, 2.2%). One hundred and seventy-seven of the 224 cases (177/224, 79.0%) were positive for NTRK. Fifty cases were analyzed using fluorescence in situ hybridization. Among them, five DMGs (positive rate, 10.0%) were NTRK fusion positive. This study showed that there were no differences between adult and pediatric DMGs in histological grading, expression of NTRK, and NTRK gene fusion. One hundred and fifty-nine patients were included in the follow-up analysis (P>0.05). During the follow-up period, 109/159 patients (69.6%) died of the disease, with a median survival time of 12 months (range 1 to 55 months). Univariate log-rank analysis showed that age, location, surgical procedure and postoperative adjuvant therapy were associated with overall survivals of the DMG patients (P<0.05). Conclusions: The prognosis of DMG is poor overall. There are differences between adult and pediatric DMGs in anatomic location and prognosis, but not in other features. NTRK1 gene fusion is detected in 10.0% of the tumors. It suggests that TRK inhibitor might be a choice for treating DMG.

First Measurement of High-Energy Reactor Antineutrinos at Daya Bay.

This Letter reports the first measurement of high-energy reactor antineutrinos at Daya Bay, with nearly 9000 inverse beta decay candidates in the prompt energy region of 8-12 MeV observed over 1958 days of data collection. A multivariate analysis is used to separate 2500 signal events from background statistically. The hypothesis of no reactor antineutrinos with neutrino energy above 10 MeV is rejected with a significance of 6.2 standard deviations. A 29% antineutrino flux deficit in the prompt energy region of 8-11 MeV is observed compared to a recent model prediction. We provide the unfolded antineutrino spectrum above 7 MeV as a data-based reference for other experiments. This result provides the first direct observation of the production of antineutrinos from several high-Q_{ß} isotopes in commercial reactors.

[A real-world study of the efficacy and safety of sofosbuvir and velpatasvir in the treatment of HCV-infected patients in a county in northern China].

Objective: To evaluate the real-world efficacy and safety of sofosbuvir and velpatasvir (SOF/VEL) tablets in the treatment of Chinese patients with chronic HCV infection. Methods: An open-label, single-center, prospective clinical study was conducted in a county in northern China. A total of 299 cases were enrolled. Of these, 161 cases with chronic hepatitis C and 73 cases with compensated cirrhosis received SOF/VEL for 12 weeks. 65 cases with decompensated cirrhosis received SOF/VEL combined with ribavirin for 12 weeks (22 cases) or SOF/VEL for 24 weeks (43 cases). Virological indicators, liver and renal function indexes, and liver stiffness measurement were detected at baseline, the fourth week of treatment, the end of treatment, and the 12-weeks of follow-up. Adverse reactions and laboratory abnormalities were observed during the course of treatment . The primary endpoint was undetectable rate of HCV RNA (SVR12) at 12 weeks of follow-up with the use of modified intention-to-treat (mITT) approach. Measurement data between two groups were compared using t-test. One Way ANOVA was used for comparison between multiple groups. Enumeration data were analyzed by chi-square test or Fisher's exact test. Results: 291 cases had completed treatment. HCV RNA was undetectable after 12 weeks of follow-up, and the SVR12 rate was 97.3% (95% confidence interval: 95.4%-99.3%). Among them, 97.4% of genotype 1b, 96.4% of genotype 2a, and 100% of those with undetected genotype achieved SVR12. The SVR12 rates in patients with chronic hepatitis C, compensated and decompensated liver cirrhosis were 98.1%, 98.6% and 93.8%, respectively. An improvement in alanine aminotransferase, aspartate aminotransferase and other liver biochemical indicators accompanied with virological clearance and reduced liver stiffness measurement was observed in patients with compensated cirrhosis, with statistically significant difference. There was no significant abnormality in renal function before and after treatment. The most common adverse reactions were fatigue, headache, epigastric discomfort and mild diarrhea. The overall adverse reactions were mild. One patient died of decompensated liver cirrhosis combined with massive upper gastrointestinal bleeding, which was unrelated to antiviral treatment. Four patients discontinued treatment prematurely due to adverse events. Relapse was occurred in four cases, and drug-resistance related mutations were detected in three cases. Conclusion: Sofosbuvir and velpatasvir tablets in Chinese HCV-infected patients with different genotypes, different clinical stages or previously treated with pegylated interferon combined with ribavirin resulted in higher SVR12, indicating that the treatment safety profile is good.

[Pediatric SMARCB1/INI1-deficient poorly differentiated chordoma of the skull base: report of five cases and review of literature].

Objective: To investigate the clinicopathological characteristics and differential diagnosis of pediatric SMARCB1/INI1-deficient poorly differentiated chordoma (PDC) of the skull base. Methods: Five cases of SMARCB1/INI1-deficient PDC were identified in 139 cases of chordoma diagnosed in Sanbo Brain Institute, Capital Medical University, Beijing, China from March 2017 to March 2021. The clinical and imaging data of the 5 PDCs were collected. H&E and immunohistochemical staining, and DNA methylation array were used, and the relevant literatures were reviewed. Results: All 5 PDCs were located at the clivus. The average age of the patients was 6.4 years, ranging from 3 to 16 years. Three patients were female and two were male. Morphologically, in contrast with classical chordomas, they presented as epithelioid or spindle tumor cells organized in sheets or nests, with necrosis, active mitoses, and infiltration into surrounding tissue. All cases showed positivity of CKpan, EMA, vimentin and brachyury (nuclear stain), and loss of nuclear SMARCB1/INI1 expression. S-100 protein expression was not frequent (2/5). Ki-67 proliferative index was high (20%-50%). All cases had over-expressed p53. It was necessary to differentiate SMARCB1/INI1-dificient PDC from SMARCB1/INI1-dificient tumors occurring at skull base of children or the tumors with epithelial and spindle cell morphological features. The 3 PDCs with DNA methylation testing showed the methylation profiles different from the pediatric atypical teratoid/rhabdoid tumors. They formed an independent methylation profile cluster. The clinical prognosis of the 5 patients was poor, and the overall survival time was 2-17 months. Conclusions: PDC is a special subtype of chordoma, which often affects children and occurs in the clivus. The PDC shares epithelioid or spindle cell morphologic features which are different from the classic chordoma. Besides the typical immunohistochemical profile of chordoma, PDC also has loss of nuclear SMARCB1/INI1 expression and distinct epigenetic characteristics.

[Rifaximin improves clinical symptoms and short-term survival in cirrhotic patients with refractory type ascites].

Objective: To investigate the effects of rifaximin treatment outcomes on complications and 24-week survival rate in cirrhotic patients with refractory type ascites. Methods: A retrospective cohort study was conducted on 62 cases with refractory ascites, and were divided into rifaximin treatment group (42 cases) and control group (20 cases) according to the actual treatment conditions. Rifaximin treatment group patients were administered oral rifaximin-α 200 mg four times daily for 24 consecutive weeks, and the other treatments were basically the same in both groups. Fasting body weight, ascites, complications and survival rate between the two groups were observed. Measurement data of the two groups using t-test, Mann-Whitney U test, and repeated measures analysis of variance were compared. χ2 test or Fisher's exact test were used to compare the enumeration data between the two groups. Kaplan-meier survival analysis was used to compare the survival rates. Results: At 24-week of rifaximin treatment, patients average body weight was reduced by 3.2 kg and the average ascites depth was reduced by 4.5 cm with B-ultrasound measurement, while in the control group at 24-week, the average body weight was reduced by 1.1 kg and the average ascites depth was reduced by 2.1 cm with B-ultrasound measurement, and the differences between the two groups were statistically significant (F=4.972, P=0.035; F=5.288, P=0.027). Hepatic encephalopathy incidence of grade II or above, hospitalization rates due to exacerbation of ascites, and spontaneous bacterial peritonitis were significantly lower in the rifaximin treatment group than those in the control group (2.4% vs. 20.0%, χ2=5.295, P=0.021; 11.9% vs. 50.0%, χ2=10.221, P=0.001; 7.1% vs. 25.0%, χ2=3.844, P=0.050). The 24-week survival rate was 83.3% in the rifaximin treatment group and 60.0% in the control group, P=0.039. Conclusion: Rifaximin treatment can significantly improve ascites symptoms, reduce the incidence of cirrhosis complications and improve the 24-week survival rate in cirrhotic patients with refractory type ascites.

Ultrasonic evaluation of systemic and renal perfusion in sepsis patients before and after fluid resuscitation.

OBJECTIVE: This study aimed to explore the significance of renal Doppler ultrasound in evaluating systemic and renal perfusion in sepsis patients before and after fluid resuscitation. PATIENTS AND METHODS: Forty sepsis patients admitted to the Department of Intensive Medicine and intensive care unit (ICU) of the Fourth Hospital of Hebei Medical University from June 2014 to December 2014 were enrolled in this study, and 35 patients were included in the final analysis. These patients were divided into positive and negative fluid responsiveness groups. They were also divided into an acute kidney injury (AKI) group and a non-AKI group according to changes in creatinine and urine volume. The correlations of the changes in hemodynamics before and after fluid resuscitation in each group with the changes in renal resistance index (RRI) and renal blood flow (RBF) grades were evaluated. RESULTS: Before and after fluid resuscitation, the heart rate (HR), blood creatinine (Cre), and lactate (Lac) levels of all patients, including the patients in the positive fluid responsiveness group decreased, and the stroke volume (SV) and central venous pressure (CVP) increased. Only HR decreased in the negative fluid responsiveness group. In the AKI group, HR, Cre, and Lac decreased, while in the non-AKI group, HR decreased, but CVP and SV increased. There were differences between HR, Lac, and change rate of Lac (Lac%) after fluid resuscitation for the positive and negative fluid responsiveness groups. There was no statistical difference between the RRI values of each group before and after fluid resuscitation. The RRI values of the AKI group were higher than those of the non-AKI group, while the AKI group's RBF grades were lower than those of the non-AKI group. The change rate of RRI (RRI%) was higher in the AKI group than in the non-AKI group. Except for the negative fluid responsiveness group, the RBF grade of each group increased. CONCLUSIONS: The approach of RBF classification based on Doppler ultrasound can be used to evaluate the systemic and renal perfusion of patients with severe sepsis before and after fluid resuscitation, while the RRI value cannot be used for evaluation. However, the RRI value can be used as a dynamic index for the evaluation of renal perfusion in patients with AKI.

[Mid- and long-term results of endovascular aneurysm repair for abdominal aortic aneurysms: a single center's experience for 10 years].

Objective: To examine the mid- and long-term outcomes of endovascular aneurysm repair (EVAR). Methods: This was a retrospective cohort study of 540 patients with abdominal aortic aneurysm who received EVAR at Department of Vascular Surgery, The First Affiliated Hospital, Sun Yat-sen University from January 2009 to December 2018. There were 503 males and 37 females, aged of (69±8) years (range: 44 to 87 years). Clinical data including concomitant disease, aneurysm size and surgical data were collected and patients were followed up after operation. The cumulative survival rate was assessed using the Kaplan-Meier estimator and multivariate Cox regression was used to analyze the independent prognosis factors. Results: The technical success rate was 91.1% (492/540). The perioperative mortality rate was 1.3% (7/540) and the follow-up rate was 91.7% (489/533). The median follow-up time was 45(63) months (range: 1 to 133 months). The all-cause mortality rate was 21.3% (104/489) and the aneurysm-related mortality rate was 6.3% (31/489) during follow-up period. The overall cumulative survival rate of 1-, 3-, 5- and 10-year were 95.1%, 84.0%, 69.5% and 38.6%, respectively, while freedom from aneurysm-related death were 98.4%, 93.3%, 88.4% and 84.4%. During the follow-up period, the complications rate was 9.0% (44/489), and the re-intervention rate was 4.9% (24/489). Cox regression analysis showed that elder age (HR=2.15, 95%CI: 1.41 to 3.26, P<0.01), preoperative aneurysm rupture (HR=2.72, 95%CI: 1.78 to 4.15, P<0.01) and short neck aneurysm (HR=1.97, 95%CI: 1.07 to 3.61, P=0.029) were independent prognosis factors for long-term survival after EVAR. Connclusion: EVAR has low perioperative mortality, high technical success rate, and satisfactory mid-and long-term outcomes.

Extraction of the

This Letter reports the first extraction of individual antineutrino spectra from ^{235}U and ^{239}Pu fission and an improved measurement of the prompt energy spectrum of reactor antineutrinos at Daya Bay. The analysis uses 3.5×10^{6} inverse beta-decay candidates in four near antineutrino detectors in 1958 days. The individual antineutrino spectra of the two dominant isotopes, ^{235}U and ^{239}Pu, are extracted using the evolution of the prompt spectrum as a function of the isotope fission fractions. In the energy window of 4-6 MeV, a 7% (9%) excess of events is observed for the ^{235}U (^{239}Pu) spectrum compared with the normalized Huber-Mueller model prediction. The significance of discrepancy is 4.0σ for ^{235}U spectral shape compared with the Huber-Mueller model prediction. The shape of the measured inverse beta-decay prompt energy spectrum disagrees with the prediction of the Huber-Mueller model at 5.3σ. In the energy range of 4-6 MeV, a maximal local discrepancy of 6.3σ is observed.

[Application of adaptive statistical iterative reconstruction veo and 80 kv in renal computed tomography angiography].

Objective: To explore the application of adaptive statistical iterative reconstruction Veo (ASIR-V) and 80 kV in renal computed tomography angiography(CTA). Methods: Eighty patients with renal computed tomography angiography were prospectively collected from April 2018 to July 2018 in the Affiliated Hospital of Shaanxi University of Chinese Medicine and randomly divided into group A and group B. The patients in group A adopted tube voltage 120 kV and contrast agent concentration 600 mgI/kg and reconstructed with filtered back projection (FBP), while the patients in group B were scanned with tube voltage 80 kV and contrast agent concentration 350 mgI/kg and reconstructed with FBP and ASIR-V from 10% to 100% with 10% interval. The CT values and standard deviation (SD) of the right renal artery, left renal artery were measured respectively to calculate the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR).The image quality of renal CTA was subjectively scored by two experienced radiologists blindly using a 5-point criteria.The contrast agent,CT volume dose index(CTDI(vol)) and dose length product(DLP) in both groups were recorded and the effective radiation dose(ED) was calculated. Results: The ED ((2.11±0.19)mSv) and contrast agent ((21.9±3.0)g) in group B were 65.1% (P<0.05) and 42.2% (P<0.05) lower than those in group A ((6.04±1.89)mSv and (38.0±3.8)g).With the increase of ASIR-V percentage in group B, CT values showed no significant difference, SD values gradually decreased, SNR values and CNR values gradually increased.The CT values with different reconstruction algorithm showed no statistically significant difference (all P>0.05) between group A and group B. The SD values with 40%ASIR-V to 100%ASIR-V reconstruction in group B were significantly lower than those of group A (all P<0.05).The SNR values with 50% ASIR-V to 100% ASIR-V reconstruction and CNR values with 70%ASIR-V to 100%ASIR-V were significantly higher than those of group A(all P<0.5).Two radiologists had excellent consistency in subjective scores of image quality for renal CTA(all kappa>0.75, P<0.05). The subjective scores with 60% ASIR-V to 90% ASIR-V in group B were significantly higher than those in group A (P<0.05), of which 70%ASIR-V reconstruction achieved the highest subjective score for renal CTA. Conclusion: ASIR-V and 80 kV can significantly reduce radiation dose (about 65.1%) and contrast agent (about 42.2%) in renal CTA, ASIR-V reconstruction can significantly improve the image quality of renal CTA, of which 70% ASIR-V reconstruction achieved the best image quality in 80 kV renal CTA.

[Association of single nucleotide polymorphisms of TBX5 gene and environmental exposure index with susceptibility to oral cancer].

Objective: To explore the association of TBX5 polymorphisms and environmental exposure index with susceptibility to oral cancer. Methods: A case-control study was conducted to collect 300 oral cancer patients hospitalized in the Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital of Fujian Medical University from September 2010 to December 2016. A total of 445 non-tumor patients were selected as the control group. Questionnaires were used to collect the information of all subjects and 5 ml peripheral blood was collected to detect single nucleotide polymorphisms (SNPs) of the rs10492336 locus of TBX5 gene. According to the environmental exposure index score, subjects were divided into two groups, low risk group (0-2.31) and high risk group (2.32-11.76). To analyze the association of TBX5 gene rs10492336 SNPs, environmental exposure index and oral cancer and its interactions. Results: The age of all subjects in the case group and control group were (56.19±13.10) years and (54.56±12.48) years old. Compared with CC genotype, the OR (95%CI) values of the co-dominant genetic model AC genotype and the dominant genetic model AC+AA genotype were 0.69 (0.49-0.98) and 0.70 (0.51-0.97), respectively. Compared with the low risk group, the OR (95%CI) risk of oral cancer in the high risk group was 3.72 (2.55-5.43). The results of gene-environment interaction analysis showed that compared with the group with CC genotype and high risk of environmental exposure index, the OR (95%CI) value of oral cancer in the group with AC+AA genotype and low risk of environmental exposure index was 0.18(0.10-0.31). Furthermore there was a multiplicative interaction between rs10492336 SNPs and environmental exposure index (ß=-0.405, P<0.001). Conclusion: This study suggests that the TBX5 gene rs10492336 SNPs and environmental exposure index were associated with oral cancer. And there was a multiplication interaction between rs10492336 SNPs and environmental exposure index.

[Association between the time of neutrophils to the lowest and prognosis of patients with esophageal squamous cell carcinoma treated with non-operative therapy].

Objective: To investigate the association between the time of neutrophils to the lowest and prognosis of patients with esophageal squamous cell carcinoma (ESCC) treated with non-operative therapy. Methods: The clinical data of 325 non-operative treated ESCC patients were collected in this study. The X-title software was applied to establish optimal threshold of neutrophil reduction to the lowest value. According to the optimal threshold, the patients were divided into early group (115 cases) and late group (210 cases). The clinical features and survival time of the two groups were compared, and the factors of prognosis were analyzed by Cox regression model with univariate and multivariate analysis. Results: The X-title software demonstrated the optimal cutoff values for the time of neutrophils to the lowest was 39 days. The median overall survival time was 21.0 months in the early group which was significantly higher than that in the late group (16.0 months). Multivariate Cox regression analysis showed that the treatment methods and the time of neutrophils to the lowest were independent factors for overall survival of patients with ESCC treated by non-surgical therapy. Compared with radiotherapy alone, concurrent chemoradiation could benefit the survival (HR=0.64, P=0.026). The prognosis of patients in the late group of neutrophils to the lowest (HR=1.38, P=0.038) was poor compared with the early group. Furthermore, stratified by treatment methods, the overall survival of two groups showed statistically significant difference only in patients received concurrent chemoradiation. The mortality risk in the late group was higher than that in the early group (HR=3.53, P=0.010). Conclusion: The time of neutrophils to the lowest is an independent prognosis factor for non-operative treated ESCC patients. The prognosis of patients in the early group is better than that in the late group.

MiR-940 regulates angiogenesis after cerebral infarction through VEGF.

OBJECTIVE: The aim of this study was to investigate whether miR-490 was involved in the regulation of angiogenesis after cerebral infarction by regulating vascular endothelial growth factor (VEGF) expression. MATERIALS AND METHODS: Sprague Dawley (SD) rats were used to establish a middle cerebral artery infarction model. Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to detect the expression levels of miR-940 in serum and brain tissues at 1, 3, and 7 days after cerebral infarction. Meanwhile, miR-940 expression in brain microvascular endothelial cells (BMECs) after Oxygen-Glucose Deprivation (OGD) for 2, 4, 6 hours was measured by qRT-PCR, respectively. The cells were transfected with miR-940 mimics/inhibitor to achieve miR-940 overexpression or inhibition. Subsequently, the angiogenesis and proliferation ability of the cells was evaluated by 5-ethynyl-2'-deoxyuridine (EDU) assay. Besides, the mRNA and protein expression levels of VEGF after miR-940 transfection were detected by Western blot and qRT-PCR, respectively. Finally, recovery experiment was used to determine whether miR-940 affected angiogenesis and proliferation of BMECs by regulating VEGF expression. RESULTS: The expression level of miR-940 in serum and brain tissues of rats was markedly decreased at 1, 3, and 7 days after cerebral infarction, which was then recovered on the 7th day. After 2, 4, and 6 hours of glucose and oxygen deprivation in BMECs, the expression level of miR-940 was significantly decreased. However, it was evidently recovered after 6 hours. After miR-940 over-expression in BMECs, the angiogenesis and proliferation of BMECs were remarkably inhibited. Conversely, miR-940 inhibitor transfection could significantly promote the formation of luminal cells and the proliferation of BMECs. QRT-PCR results showed that miR-940 overexpression down-regulated the expression level of VEGF, and the same findings were observed at the protein level. Further studies revealed that VEGF could reverse the inhibitory effect of miR-940 on lumen formation and cell proliferation in BMECs. CONCLUSIONS: The expression of miR-940 was downregulated in cerebral infarction. The low expression of miR-940 could promote the angiogenesis ability of cerebral microvascular endothelial cells after cerebral infarction, which might be resulted from the inhibitory effect of miR-940 on VEGF.

[Study on characteristics and prognosis of organ failure in patients with hepatitis B virus-associated acute-on-chronic liver failure].

Objective: To evaluate the incidence, and the characteristics of organ failure in relationship to prognosis in hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF) patients using chronic liver failure-sequential organ failure assessment (CLIF-SOFA) score for judgments of clinical treatment and prognosis. Methods: Clinical data of 316 patients who were diagnosed as HBV-ACLF during hospitalization from February 2015 to February 2016 were retrospectively analyzed. Intrahepatic and extrahepatic organ failures were assessed according to CLIF-SOFA score, and the relationship between clinical characteristics and prognosis was analyzed. Continuity variables were analyzed by analysis of variance, or Kruskal-Wallis H test. Comparison of the categorical data were done using χ (2) or Fisher's exact test, and the predictive efficacy of various prognostic scores was compared using the area under the receiver operating characteristic curve (AUROC) and Z-test. Results: Of 316 cases (87.3% men) of HBV-ACLF, the mean age was (45 ± 11) years old. 78.8% of patients with underlying liver disease had hepatitis B virus induced cirrhosis. Mortality rates in patients without liver transplantation at 28 days, 90 days and 180 days were 20.5% (63/307), 36.7% (110/300) and 39.2% (116/296), respectively. According to the CLIF-SOFA score, 89.9% (284 patients) had organ failure at baseline, of which 97.5% had liver failure (Total bilirubin ≥ 12 mg/dl) and only 2.5% had coagulation, kidney, circulation or respiratory failure without liver failure. Besides liver failure, the incidence of extrahepatic organ failure was coagulation (23.1%), kidney (5.7%), brain (3.8%), circulation (1.3%) and respiratory failure (0.3%). With increasing number of organ failure, the mortality rate of two and three or more organ failures were 69.6% and 69.2%, respectively, which was significantly higher than that of single organ failure and non-organ failure patients (27% and 6.9%, respectively; P < 0.001). Liver failure with coagulation failure (International normalized ratio≥2.5 or platelet count≤20×10(9)/L) had worst prognosis with a mortality rate of up to 75% at 90 days. Conclusion: According to the CLIF-SOFA score, the main organ failure in patients with HBV-ACLF in China is liver failure. The mortality rate in patients with two or more organ failures is as high as 70% within 3 months. Therefore, timely manner liver transplantation should be considered.

Ipriflavone promotes osteogenesis of MSCs derived from osteoporotic rats.

OBJECTIVE: To explore whether Ipriflavone could prevent postmenopausal osteoporosis (PMOP) and improve bone quality via promoting osteogenesis of bone marrow-derived mesenchymal stem cell (MSCs). MATERIALS AND METHODS: MSCs were extracted from rats and identified using flow cytometry. Osteogenic specific genes and adipogenic specific genes in MSCs were detected by quantitative Real-time polymerase chain reaction (qRT-PCR). The effect of Ipriflavone on osteogenesis was detected by CCK-8 (cell counting kit-8) assay, ALP activity detection, alizarin red staining and Western blot, respectively. Furthermore, ovariectomized PMOP rat model was constructed. The effects of Ipriflavone on osteogenesis, BMD and bone biomechanical properties of ovariectomized rats were detected. RESULTS: MSCs derived from ovariectomized rats exerted multiple differentiation potentials. CCK-8 assay indicated that 0.8 µM Ipriflavone were the maximal dose that did not affect MSCs proliferation, which was selected for the following experiments. In vitro researches demonstrated that Ipriflavone remarkably promoted MSCs osteogenesis. In vivo results indicated that BMD, BV/TV, Tb.N and Tb.Th were decreased in ovariectomized rats than those of rats in sham group. Ipriflavone treatment remarkably prevented osteoporosis via promoting MSCs osteogenesis in ovariectomized rats. CONCLUSIONS: Ipriflavone prevents postmenopausal osteoporosis, improves bone quality and protects bone tissue via promoting MSCs osteogenesis.

[Technical specification for clinical application of critical ultrasonography].

Critical ultrasonography(CUS) is different from the traditional diagnostic ultrasound, the examiner and interpreter of the image are critical care medicine physicians. The core content of CUS is to evaluate the pathophysiological changes of organs and systems and etiology changes. With the idea of critical care medicine as the soul, it can integrate the above information and clinical information, bedside real-time diagnosis and titration treatment, and evaluate the therapeutic effect so as to improve the outcome. CUS is a traditional technique which is applied as a new application method. The consensus of experts on critical ultrasonography in China released in 2016 put forward consensus suggestions on the concept, implementation and application of CUS. It should be further emphasized that the accurate and objective assessment and implementation of CUS requires the standardization of ultrasound image acquisition and the need to establish a CUS procedure. At the same time, the standardized training for CUS accepted by critical care medicine physicians requires the application of technical specifications, and the establishment of technical specifications is the basis for the quality control and continuous improvement of CUS. Chinese Critical Ultrasound Study Group and Critical Hemodynamic Therapy Collabration Group, based on the rich experience of clinical practice in critical care and research, combined with the essence of CUS, to learn the traditional ultrasonic essence, established the clinical application technical specifications of CUS, including in five parts: basic view and relevant indicators to obtain in CUS; basic norms for viscera organ assessment and special assessment; standardized processes and systematic inspection programs; examples of CUS applications; CUS training and the application of qualification certification. The establishment of applied technology standard is helpful for standardized training and clinical correct implementation. It is helpful for clinical evaluation and correct guidance treatment, and is also helpful for quality control and continuous improvement of CUS application.

[A novel prognostic index for oral cancer in Fujian province].

Objective: To explore the survival factors and construct a prognostic index (PI) for oral squamous cell carcinoma (OSCC). Methods: From January 2004 to June 2016, a total of 634 patients with pathologically confirmed OSCC were recruited in a hospital of Fujian. The clinical and follow-up data of all the patients with pathologically confirmed OSCC were collected to identify the factors influencing the prognosis of OSCC. All the patients were randomly divided into two groups: modeling group (modeling dataset, n=318) and validation group (validation dataset, n=316). Randomization was carried out by using computer-generated random numbers. In the modeling dataset, survival rates were calculated using Kaplan-Meier method and compared using the log-rank test. Cox regression model was used to estimate the hazard ratio (HRs) and 95% confidence intervals (CIs) of prognosis factors. An PI for OSCC patients prognostic prediction model was developed based on ß value of each significant variable obtained from the multivariate Cox regression model. Using the tertile analysis, patients were divided into high-risk group, moderate-risk group, and low-risk group according to the PI, the Akaike information criterion (AIC) and Harrell's c-statistic (C index) were used to evaluated the model's predictability. Results: Results from the multivariate Cox regression model indicated that aged ≥55 years (HR=2.22, 95%CI: 1.45-3.39), poor oral hygiene (HR=2.12, 95%CI: 1.27-3.54), first diagnosis of lymph node metastasis (HR=5.78, 95%CI: 3.60-9.27), TNM stage Ⅲ-Ⅳ (stage Ⅰ as reference) (HR=2.43, 95%CI: 1.10-5.37) and poor differentiation (well differentiation as reference) (HR=2.53, 95%CI: 1.60-4.01) were the risk factors influencing the prognosis of OSCC. The PI model had a high predictability in modeling group and validation group (AIC and C index were 1 205.80, 0.700 2 and 1 150.47, 0.737 3). Conclusion: Age, poor oral hygiene, first diagnosis of lymph node metastasis, TNM stage and histological grade were factors associated with the prognosis of OSCC, and the PI model has a certain significance in the clinical treatment of OSCC.